title: In vitro-induced cell-mediated immune deviation to encephalitogenic antigens.
abstract: The injection of antigens into the Anterior Chamber (AC) of the eye induces Anterior Chamber Associated Immune Deviation (ACAID), which is a potent form of immune deviation that is largely attributed to the effect of TGFβ2 in the aqueous humor on ocular antigen-presenting cells (APCs). ACAID antigen presentation via APCs and B cells leads to the generation of antigen-specific T regulatory cells. The encephalitogenic antigens Myelin oligodendrocyte glycoprotein (MOG) and Myelin basic protein (MBP) have an obvious clinical relevance. We hypothesized that the intravenous injection of in vitro-generated ACAID APCs or in vitro-generated ACAID B cells specific to the encephalitogenic antigens MOG35-55/MBP induces specific peripheral tolerance in recipient BALB/c mice. We examined the suppression of MOG35-55-specific/MBP-specific inflammatory responses using delayed-type hypersensitivity (DTH) assays and Local Adoptive Transfer (LAT) assays. Results indicated that MOG35-55-specific/MBP-specific tolerance was generated after the intravenous injections of MOG35-55-specific/MBP-specific ACAID APCs, MOG35-55-specific/MBP-specific ACAID B cells, and MOG35-55-specific/MBP-specific ACAID T regulatory cells. The specific immune deviation was in vitro-induced, cell-mediated, and specific to the encephalitogenic antigens MOG35-55/MBP. This in vitro-mediated approach for the generation of MOG35-55/MBP-specific tolerance opens up avenues for the application of ACAID as a tool for the therapy of Multiple Sclerosis, Schizophrenia, and other diseases.
authors.affiliation: Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, United States.
authors.forename: Shukkur M
authors.initials: SM
authors.lastname: Farooq
authors.forename: Hossam M
authors.initials: HM
authors.lastname: Ashour
mesh_terms: D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D004676:Myelin Basic Protein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)
keywords: AC; ACAID; APCs; Anterior Chamber; Anterior Chamber Associated Immune Deviation; B cells; DTH; Immune tolerance; LAT; MBP; MOG; Myelin; Myelin basic protein; Myelin oligodendrocyte glycoprotein; TGF-β2; Transforming growth factor beta; antigen presenting cells; delayed-type hypersensitivity; local adoptive transfer